Molecular/antigenic mimicry and immunological cross-reactivity explains SARS-CoV-2-induced autoimmunity

Abstract

COVID-19 pandemic is over, but its effects on chronic illnesses remain a challenging issue. Understanding the influence of SARS-COV-2-mediated autoimmunity and overt autoimmune disease is of paramount importance, as it can provide a critical mass of information regarding both infection-mediated (and vaccination-induced) autoimmune phenomena in susceptible individuals during the disease course, and short or long-term post-disease sequelae. The high prevalence of organ and non-organ specific autoantibody positivity in patients with COVID-19 led to studies attempting to delineate the origin and the underlying mechanism responsible for their induction nature, identifying novel autoantigens, and the self-epitope sequences which could be the impetus for the initiating autoreactive responses. Herein, we provide a meticulous review of the studies reporting those mimicking sequences that have been experimentally validated, based on the assumption that molecular mimicry and immunological crossreactivity may account for autoantibody development. Most reports are based on bioinformatics approaches, and only a disproportionally small number of studies currently demonstrate immunological crossreactivity. We took the opportunity to further review and searched for the linear human epitope sequences of human, through the epitopes deposited at the Immune Epitope Database. This included an analysis of autoimmune disease as the disease data to comprehensively understand the subject matter. The critical overview of the findings underscore the urgent and immense need for further research to gain a comprehensive understanding of the mechanisms involved and the anticipated appraisal that molecular mimicry and immunological crossreactivity is indeed central to the loss of immunological tolerance during SARS-COV-2 infection.